The eye relies on the aqueous humor for the nutrition of the cornea, lens, vitreous and trabecular meshwork, as well as the removal of waste products from these tissues. Steady formation and discharge of the aqueous maintains the intraocular pressure and the optical shape of the eye. A number of drugs commonly used in the treatment of glaucoma lower the intraocular pressure by suppressing the rate of aqueous formation. The ciliary body epithelium is responsible for the formation of aqueous humor and is the target of these drugs. Our objective in this project is to characterize in detail the pharmacology and physiology of drug-induced responses and increases in second messengers in the ciliary body. We are particularly interested in the role of Ca2+. Our previous studies on intact ciliary body, as well as experiments of others on dissociated cells have shown that many drugs act on the cells of the ciliary body by increasing the intracellular Ca2+ concentration. We shall use fluorescence ratio -Imaging on intact and undissociated ciliary body epithelial cells to study the pharmacology and physiology of the Ca2+ rise in some detail. We want to know which receptors are responsible for increases in Ca2+. We shall use intracellular recording on intact tissue and patch-clamp recording on dissociated cells to identify influx pathways for Ca2+. We shall then attempt to study the ion channels and transporters modulated by the Ca2+ rise. Our hope is that we can identify pathways for the modulation of intracellular Ca2+ concentration and aqueous production, which may provide new mechanisms for clinical intervention.